Diabetes negatively impacts many people's health and induces various complications. Diabetes is divided into type 1 diabetes and type 2 diabetes. Type 1 diabetes is presented when insulin is not produced due to destruction of pancreatic cells. Type 2 is presented when insulin is not produced for other reasons or the body is not responding to insulin. Type 2 diabetes is found in 90% or more of diabetic patients.
Sulfonylureas (promoting insulin secretion from pancreatic cells), biguanide (suppressing glucose production in the liver), a-glucosidase inhibitor (inhibiting glucose absorption in the intestines), thiazolidine derivatives (TZDs) and the like are currently used for the treatment of diabetes. Incretin-related drugs such as DPPIV inhibitors or Exenatide have recently entered the market.
However, these agents have unwanted side effects such as hypoglycemia, liver failure, gastrointestinal disorders and weight gain, or weak hypoglycemic function or the disadvantage that they must be used as an injection. Therefore, research has been conducted for new therapies based on a new mechanism that is able to avoid the drawbacks and side effects of existing diabetes therapies.
Recently, an insulinotropic mechanism by free fatty acid was revealed more clearly through the study of GPR40 which is a G-protein-coupled receptor. GPR40 receptor is highly expressed in the pancreas, and it has been found that ligands for GPR40 receptor are saturated free fatty acids having 12-16 carbon atoms and unsaturated fatty acids having 18-22 carbon atoms. And it is confirmed that long-chain FFAs activate GPR40 receptor depending on blood glucose concentration, thereby stimulating insulin secretion from the beta cells of the pancreas via experiments that selectively inhibit the expression of GPR40 receptor in the pancreas using siRNA (small interfering RNA) technology and that measure how insulin secretion by blood glucose changes from beta cells of the pancreas in the presence of free fatty acids.
Accordingly, GPR40 agonists have a blood glucose concentration-dependent insulin-secretion stimulating activity, and thus are useful for the treatment and prevention of diabetes and complications thereof.